study of sc-003 alone and in combination with abbv-181 in subjects with platinum-resistant/refractory ovarian cancer

Conditions: Ovarian Cancer

Summary: this is a phase 1a/1b study of sc-003 as a single agent and in combination with abbv-181 in patients with platinum-resistant/refractory ovarian cancer. sc-003 is an antibody-drug conjugate (adc) comprised of a monoclonal antibody linked to a potent chemotherapy. abbv-181 is a humanized, recombinant, mab that binds to cell surface expressed programmed cell death 1 (pd-1).

phase 1a is a dose escalation study in patients with histologically/cytologically confirmed ovarian cancer that are platinum-resistant or refractory. phase 1b is an expansion study where patients will be enrolled and treated at recommended dose and schedule based on the phase 1a.

Eligibility criteria:
inclusion criteria: * histologically or cytologically confirmed ovarian epithelial cancer * evidence of progressive disease (pd) on or within 6 months of a platinum (cisplatin or carboplatin) regimen: at least 1 prior regimen must have contained a platinum-taxane combination * measurable disease as defined by recist 1.1 * eastern cooperative oncology group (ecog) performance status of 0 or 1 * fresh or archived tumor tissue sample available for target expression analysis. \[phase 1b only: subjects' tumor tissue must test positive for target expression.\] * adequate hematologic and organ function as confirmed by laboratory values * at least 3 weeks between last systemic chemotherapy and planned start of study treatment (4 weeks for prior investigational drugs, immunotherapy, radiotherapy, or biologics) for ovarian cancer * at least 3 weeks between major surgery and planned start of study treatment; major incisions must have healed exclusion criteria: * history of prior malignancy, with the exception of the following: malignancy treated with curative intent and with no evidence of active disease present for more than 3 years prior to screening and felt to be at low risk for recurrence by treating physician; or adequately treated lentigo maligna melanoma without current evidence of disease or adequately controlled non-melanomatous skin cancer; or adequately treated cervical carcinoma in situ without current evidence of disease. * uncontrolled infection requiring systemic antibiotics/antivirals/antifungals * evidence of complete or partial bowel obstruction * patients requiring iv hydration or parenteral nutrition * positive pregnancy test in females of child-bearing potential or pregnant or currently breastfeeding * known hypersensitivity to any component of study drug including potential subjects with a history of major immunologic reaction to any igg-containing agent * inability to tolerate premedication with dexamethasone * uncontrolled cardiac disease, or myocardial infarction within the last 12 months, or left ventricular ejection fraction (lvef) \ 470 msec * class ii, iii or iv heart failure as defined by the nyha functional class system * positive serology for hepatitis b or c, or known human immunodeficiency virus infection (hiv) * previous treatment with a pyrrolobenzodiazepine (pbd)-based drug additional exclusion criteria for the sc-003 and abbv-181 combination treatment regimen: * history of inflammatory bowel disease * active autoimmune disease, with exceptions of psoriasis not requiring systemic treatment, vitiligo, type 1 diabetes mellitus and hypothyroidism * history of primary immunodeficiency, allogeneic bone marrow transplantation, solid organ transplantation, or previous clinical diagnosis of tuberculosis * history of immune-mediated pneumonitis * current or prior use of immunosuppressive medication within 14 days prior to the first dose of study treatment

Keywords: platinum-resistant refractory